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Saturday, 7 July, 2001, 07:09 GMT 08:09 UK
Dispute over number of human genes
Human chromosomes
Scientists are still betting on the number of genes in the human body
By BBC News Online's Helen Briggs

Two rival teams that cracked the human genome may have underestimated the number of human genes, according to a new computer analysis.

Scientists in the United States claim humans are built from 66,000 genes, nearly twice as many as the current consensus.

Some researchers are unsettled by the certainty with which the Human Genome Consortium is presenting its lower gene count

Fred Wright, Ohio State University
Two draft versions of the human genome were published in February this year, in what was hailed as a landmark in scientific achievement. The publicly funded Human Genome Project and a private US firm, Celera Genomics, put the number of human genes at around 35,000.

Now a third team, based at Ohio State University, Columbus, Ohio, has reanalysed the raw data, using a supercomputer, and come up with a higher estimate for the number of human genes.

"We ended up with a higher estimated number of genes than the other two teams because we compared 13 different gene databases to the DNA sequences in the draft genome produced by the Human Genome Project," said Bo Yuan of Ohio State University.

Dr Craig Venter
Dr Craig Venter: Head of Celera
The news that humans had 30,000 to 40,000 genes came as a surprise to many experts, when the findings were published in the scientific journals Nature and Science.

The tally was much lower than the 100,000 or more expected. Scientists now had to explain how a complex human could be built from about 35,000 genes, compared to the nematode worm with 18,000 and the fruit fly with 13,000.

One explanation for the difference between humans and fruit flies or worms is that human genes work differently and we have more control genes.

But some researchers remain unconvinced. They believe there are more human genes hidden in the genome.

The discrepancy seems to arise from the process used to analyse human genetic data. The human genome is a string of three billion DNA letters, comprising all the instructions needed to make a human being.

Sir John Sulston
Sir John Sulston: Who headed UK genome sequencing efforts
Buried within these coded instructions are the genes - "sentences" which hold the instructions for the proteins of which human tissue is made.

The genes occupy only about a hundredth of the length of the huge string of DNA, broken up into the 46 chromosomes in every cell.

To fish out the genes, which are hidden among the long continuous string of letters, scientists rely on genetic databases.
The human genome

The genome is the complete list of coded instructions needed to make a person
There are 3.1 billion letters in the DNA code in every one of the 100 trillion cells in the human body
If all of the DNA in the human body were put end to end, it would reach to the Sun and back more than 600 times.

The Ohio State University team says Celera's genome map, and particularly, the Human Genome Project map relied mainly on two databases to locate the genes. They used these two databases plus 11 others.

"We used more experimental evidence in assembling our map, and that suggests that there are probably between 65,000 and 75,000 transcriptional units," said Dr Yuan.

A transcriptional unit is a length of DNA that shows strong evidence of being a gene but which requires future verification. This is where the dispute arises.

"Some researchers are unsettled by the certainty with which the Human Genome Consortium is presenting its lower gene count," said Fred Wright of Ohio State University.

"In my view, the final number of genes - when it is known - will lie somewhere between their high of 40,000 and our value of 70,000."

But the new analysis, published on the website of the journal Genome Biology, has been dismissed by the Sanger Centre, in Cambridgeshire, UK, which was responsible for about a third of the human genome sequencing effort.

The experimental evidence actually points to 30-40,000 genes

Dr Tim Hubbard, Sanger Centre
Tim Hubbard, head of human genome analysis at the Sanger Centre, said the work was flawed.

"The experimental evidence actually points to 30-40,000 genes," Dr Hubbard told BBC News Online. "I don't believe the argument in this paper that there are a lot more genes. This is an entirely computational paper and I don't think it's very credible.

"The real test will come from experiments to see if what computers suggest are genes, are actually real genes," he added.

Arguments over how many genes it takes to build a human being look set to continue. A gene sweepstake set up by scientists attending the Cold Spring Harbor Genome Meetings in the United States is still taking entries. To date, there have been 165 bets, ranging from 27,462 to 153,478 human genes. So far, the money is on 61,710.

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